Method of improving the appearance of aging skin

ABSTRACT

A method of improving the appearance of aging skin that includes applying an effective amount of artichoke leaf extract and vitamin B3 compound in combination to a target area of skin that exhibits a sign of aging skin, and compositions that include an effective amount of artichoke leaf extract and vitamin B3 compound in combination. The composition is applied for a period of time sufficient for the combination of vitamin B3 compound and niacinamide to improve the appearance of the aging skin.

FIELD

The present invention relates to methods of improving the appearance ofaging skin, especially fine lines and wrinkles, using a synergisticcombination of artichoke leaf extract and a vitamin B₃ compound.

BACKGROUND

The epidermis, the outermost layer of the skin, comprises a cellularcontinuum of four layers: the stratum corneum, the granular layer, thespinous layer, and the basal layer. Each cellular layer in the epidermisrepresents various stages along a process in which basal epidermalkeratinocytes undergo a continuous cycle of proliferation,differentiation, and apoptosis, moving upward from the basal layer tofinally yield corneocytes. These corneocytes form the cornified layerknown as the stratum corneum.

Basal keratinocytes reside at the lower portion of the epidermis. Thesemitotically active cells undergo a proliferative cycle to generatedaughter cells that are physically dislocated upward into the spinousand granular layers and undergo the process of differentiation intocorneocytes. On passing through the spinous and granular layers, thecells undergo morphological changes that render them flatter instructure as they lose their cellular viability, undergo alternatekeratin expression profiles, and transform into cellular remnants. Onaverage, a younger-aged epidermis turns over in about one month,shedding the older cells and replacing them with newer ones, but thisprocess can increase to over forty days in older skin.

The stratum corneum's corneocytes remain connected to one other viaproteins and lipids, creating a protective barrier between the organismand its outside environment. This tightly regulated epidermalpermeability barrier functions as a physical and selective barrieragainst chemical and biological insults Important functions of thisbarrier include attenuation of the penetration of free radicals andprevention of penetration of harmful radiation, including UV radiation,into deeper layers. The stratum corneum also acts as a permeabilitybarrier and functions to prevent loss of body moisture to the outsideenvironment. Dysfunction of this barrier can lead to chronic skinconditions, diseases, and in extreme cases can even threaten theviability of the organism.

Skin aging is a multifactorial process driven by intrinsic(chronological aging) and extrinsic (environmental) factors, includingultraviolet radiation (UV) exposure (i.e., “photoaging”), environmentaltoxins, pollutants, and smoking. It is well known in the art that theability of the stratum corneum to cyclically generate new layers of skindiminishes with age so that the stratum corneum turnover rate issubstantially reduced in aged skin, with the cornified layer becominggradually thinner. This results in a reduction in the functioningcapacity of the barrier so that harmful stimuli penetrate the stratumcorneum more easily, leading to UV-damage, for example, of theunderlying dermal layers, degradation of collagen and elastin, andeventually manifests in appearance as wrinkling and skin atrophy.Thinning of the stratum corneum by the sum of intrinsic and extrinsicaging factors increases the visible appearance of fine lines andwrinkles. Further, the barrier suffers from an age-related increase inpermeability to free radicals and a reduction in the amount of lipid inthe intercellular matrix, decreasing barrier capacity to diffuse toxinsfrom deeper layers. Recovery capacity of the barrier to environmentalinsult is also substantially reduced with age.

Thus, the skin's epidermal barrier function is key to the skin's abilityto regenerate and protect itself from the appearance of aging signs suchas fine lines and wrinkles. Accordingly, it would be desirable toprovide compositions and methods of treatment that can improve theskin's epidermal functioning and thus also improve the appearance ofaging skin.

SUMMARY

In order to provide a solution to the problems above, disclosed hereinare methods of improving the appearance of aging skin. In someembodiments, the method comprises applying a composition with aneffective amount of artichoke leaf extract and an effective amount of avitamin B₃ compound to an area of aging skin for a period of timesufficient to improve the appearance of the aging skin. In someembodiments, the area of aging skin may be aging facial skin. Inparticular embodiments, improving the appearance of aging skin comprisesimproving the appearance of aging skin texture such as wrinkles, finelines, coarse deep lines, crevices, bumps; preventing loss of skinelasticity, for example, due to loss, damage and/or inactivation offunctional skin elastin, resulting in such conditions as elastosis,sagging, loss of skin recoil from deformation; and combinations thereof.

In response to the problems identified in the background, the presentinvention may take other forms. Further forms herein will be appreciatedin the detailed description that follows.

DETAILED DESCRIPTION

All percentages and ratios used herein are by weight of the totalcomposition and all measurements made are at 25° C., unless otherwisedesignated. All numeric ranges are inclusive of narrower ranges;delineated upper and lower range limits are interchangeable to createfurther ranges not explicitly delineated.

The compositions herein can comprise, consist essentially of, or consistof, the essential components as well as optional ingredients describedherein. As used herein, “consisting essentially of” means that thecomposition or component may include additional ingredients, but only ifthe additional ingredients do not materially alter the basic and novelcharacteristics of the claimed compositions or methods. As used in thedescription and the appended claims, the singular forms “a,” “an,” and“the” are intended to include the plural forms as well, unless thecontext clearly indicates otherwise.

“Additive effect” means that the effect provided by a combination ofactives is equal to or substantially equal to the sum of theirindividual effects. For example, an additive effect would bedemonstrated when a first active, which provides a 10% improvement in adesired property (e.g., inhibition of NF-κB, which is described in moredetail below), when used alone, and a second active, which provides a20% improvement in the desired property when used alone, provide a 30%improvement to the desired property when used in combination. A “morethan additive effect,” in this example, would be demonstrated when thecombination of the first and second actives improves the desiredproperty by more than 30%.

“Apply” or “application,” when referring to a composition, means toapply or spread the composition onto a human skin surface such as theepidermis.

“Cosmetic composition” means a composition suitable for topicalapplication on mammalian skin and/or other keratinous tissue such ashair and nails. Topical means the surface of the skin or otherkeratinous tissue. Cosmetic composition includes any color cosmetic,nail, or skin care product. “Skin care” means regulating and/orimproving skin condition. Nonlimiting examples of skin care includeimproving skin appearance and/or feel by providing a smoother, more evenappearance and/or feel; reducing the oily and/or shiny appearance ofskin. Non-limiting examples of cosmetic compositions include productsthat leave color on the face, such as foundation, mascara, concealers,eye liners, brow colors, eye shadows, blushers, lip sticks, lip balms,face powders, solid emulsion compact, and the like. “Skin care products”include, but are not limited to, skin creams, moisturizers, lotions, andbody washes.

“Derivative,” as used herein, includes but is not limited to, amide,ether, ester, amino, carboxyl, acetyl, and/or alcohol derivatives of agiven compound.

“Dermatologically acceptable” means that a composition or componentsdescribed are suitable for use in contact with human skin tissue withoutundue toxicity, incompatibility, instability, allergic response, and thelike.

“Effective amount” means an amount of a compound or compositionsufficient to significantly induce a positive benefit. For example, aneffective amount can mean an amount of artichoke leaf extract and/orvitamin B₃ compound sufficient to significantly induce an appearanceand/or feel benefit. Effective amount can also mean an amount ofartichoke leaf extract and/or vitamin B₃ compound in combinationsufficient to synergistically increase the inhibition of NF-κB.

“Extract” refers herein to one or more compounds separated from a plantor plant material by contacting the plant with an exogenous solvent(i.e., any solvent that is not inherently present in the plant material)in an extraction process. For example, the extract may be obtained bythe following procedure: (i) place the indicated portion of dried plantmaterial (e.g., stem, bark, leaves, etc.) in a conical glass percolator;(ii) add the indicated percentage of extraction solvent in a w/w ratioof 1 part plant material to 2 parts extraction solvent (when theindicated percentage of extraction solvent is less than 100%, theremaining solvent is water (e.g., 95% ethanol with 5% water, 50% ethanolwith 50% water, etc.)); (iii) allow the extraction to proceed for about16 to about 24 hours; (iv) collect the percolate, and repeat the aboveprocess until the resulting percolate is substantially free from plantadditional extract; (v) combine the percolates, evaporate to drynessunder reduced pressure, and store the resulting extract under nitrogenat less than 4 degrees Celsius. Extracts may be used without any furthermodification or may be modified (e.g., ethoxylated, esterified) to forma derivative material.

“Facial skin surface” means one or more of forehead, periorbital, cheek,perioral, chin, and nose skin surfaces.

“Skin care actives,” or “actives,” means compounds that, when applied tothe skin, provide a benefit or improvement to the skin.

“Synergy” and variations thereof means that the combination of vitaminB₃ compound and artichoke leaf extract provides an advantage over usingeither of the actives alone. In some embodiments, synergy may bedemonstrated by the combination of vitamin B₃ compound and artichokeleaf extract acting together to provide an anti-aging benefit that isbeyond what the combination would normally be expected to provide. Forexample, if the combination is expected to provide an additive effect,but instead provides a more than additive effect, the combination issynergistic.

“Improving the appearance of aging skin” or “improving the texture ofaging skin” means effecting a visually and/or tactilely perceptiblepositive change, or benefit, in skin texture appearance and/or feel.These terms also include preventing or delaying the appearance of one ormore textural signs of skin aging. Benefits that may be providedinclude, but are not limited to, one or more of the following: improvingthe appearance of wrinkles, fine lines, coarse deep lines, crevices,bumps; preventing loss of skin elasticity, for example, due to loss,damage and/or inactivation of functional skin elastin, resulting in suchconditions as elastosis, sagging, loss of skin recoil from deformation;and combinations thereof.

“Textural signs of skin aging” include but are not limited to, alloutward visibly and tactilely perceptible skin texture manifestations,as well as any macro- or microeffects, due to undesired changes in skintexture due to aging. These signs may result from processes whichinclude, but are not limited to, the development of texturaldiscontinuities such as wrinkles and coarse deep wrinkles, fine lines,skin lines, crevices, bumps, unevenness or roughness; loss of skinelasticity; keratoses; abnormal differentiation; hyperkeratinization;elastosis; collagen breakdown, and other histological changes in thestratum corneum, dermis, or epidermis; and combinations thereof.

I. Compositions

The present invention relates to various compositions and, morespecifically, to compositions for application to a skin surfaceincluding a wide variety of cosmetic compositions. The compositions maybe in various product forms that include, but are not limited to,solutions, suspensions, lotions, creams, gels, toners, sticks, pencil,sprays, aerosols, ointments, cleansing liquid washes and solid bars,shampoos and hair conditioners, pastes, foams, powders, mousses, shavingcreams, wipes, strips, patches, electrically-powered patches, wounddressing and adhesive bandages, hydrogels, film-forming products, facialand skin masks (with and without insoluble sheet), make-up such asfoundations, eye liners, and eye shadows, and the like. The compositionform may follow from the particular dermatologically acceptable carrierchosen, if present in the composition.

A. Artichoke Leaf Extract and Vitamin B₃ Compounds

Surprisingly, it has been discovered that vitamin B₃ compound andartichoke leaf extract, when used in combination, can provide asynergistic improvement in the inhibition of (nuclear factorkappa-light-chain-enhancer of activated B cells) (“NF-κB”). NF-κB is aprotein complex found in almost all animal cell types and is known to beinvolved in a variety of biological process such as, for example, DNAtranscription, cellular responses to stimuli such as stress, cytokines,free radicals, ultraviolet irradiation, oxidized LDL, and bacterial orviral antigens. NF-κB's recognized involvement in biochemical pathwaysassociated with skin health and aging make it a suitable indicator ofthe predictive anti-aging activity of skin care actives. In particular,NF-κB's is known to be involved in the inflammation pathway, which isassociated with the skin's barrier function as well as its ability toregenerate and protect itself from the textural signs of skin aging.Accordingly, suitable compositions herein include an effective amount ofartichoke leaf extract and vitamin B₃ compound in combination. As usedherein, “in combination” means present in the same composition (e.g., asa blend), present in different compositions but appliedcontemporaneously (e.g., close enough in time to result in the combinedsynergistic benefit of the two materials), or combinations thereof.

The amount of artichoke leaf extract that is “effective” can differ fromone particular source (e.g., manufacturer) of extract to another, andcan be determined by the skilled artisan based upon the particularextract product's level of activity (e.g., level of active componentspresent). As with any extract, the concentration of active components inthe particular extract product to be used will depend on factors such asthe final dilution volume of the extract product, the particularextraction method employed, the natural range of variation amongindividual plants, and other common factors known to those skilled inthe art.

Artichoke leaf extract (INCI Name: Cynara scolymus extract; CAS number:84012-14-6) suitable for use herein may be derived from the long, deeplyserrated basal leaves of the artichoke plant. These leaves containhigher concentrations of biologically active compounds, such as caffeicacid derivatives (e.g., cynarin); flavonoids; and sesquiterpene lactones(e.g., cynaropicrin). It can be preferable to dry the leaves beforeextraction in order to achieve greater potency of certain activematerials. For example, cynarin is found only in trace amounts in thefresh leaves, but is formed by natural chemical changes that take placeduring drying and extraction of the plant material. The artichoke leafextract may include other suitable materials such as, for example,water, thickeners, humectants, solvents, solubilizers, etc. Theartichoke leaf extract can be prepared by suitable processes known inthe art. An example of a commercially available artichoke leaf extractsuitable for use herein is Biobenefity™, made by Ichimaru Pharcos Corp.(Gifu, Japan). In some embodiments, the composition may includeartichoke leaf extract in an amount of from 0.0001% to 15%, from 0.0002%to 10%, from 0.001% to 15%, from 0.025% to 10 from 0.05% to 10%, from0.05% to 5%, or even from 0.1% to 5%, by weight of the totalcomposition.

The present compositions include a vitamin B₃ compound. As used herein,“vitamin B₃ compound” means a compound having the formula:

wherein R is —CONH₂ (i.e., niacinamide), —COOH (i.e., nicotinic acid) or—CH₂OH (i.e., nicotinyl alcohol); derivatives thereof; and salts of anyof the foregoing. The vitamin B₃ compound may be present at an amount offrom 0.0001% to 15%, from 0.0002% to 10%, from 0.001% to 15%, from0.025% to 10 from 0.05% to 10%, from 0.05% to 5%, or even from 0.1% to5%, by weight of the total composition. A particular suitable vitamin B₃compound is Niacinamide PC brand Niacinamide available from DSM.

Dermatologically Acceptable Carrier

The compositions herein may include a dermatologically acceptablecarrier (“carrier”) that provides a suitable matrix to store and deliverthe actives (i.e., artichoke leaf extract and vitamin B₃ compound) andother optional ingredients. The phrase “dermatologically acceptablecarrier”, as used herein, means that the carrier is suitable for topicalapplication to the keratinous tissue, has good aesthetic properties, iscompatible with the actives in the composition, and will not cause anyunreasonable safety or toxicity concerns. In one embodiment, the carrieris present at a level of from about 50% to about 99%, about 60% to about98%, about 70% to about 98%, or, alternatively, from about 80% to about95%, by weight of the composition.

The carrier can be in a wide variety of forms. Non-limiting examplesinclude simple solutions (e.g., aqueous, organic solvent, or oil based),emulsions, and solid forms (e.g., gels, sticks, flowable solids, oramorphous materials). In certain embodiments, the dermatologicallyacceptable carrier is in the form of an emulsion. Emulsion may begenerally classified as having a continuous aqueous phase (e.g.,oil-in-water and water-in-oil-in-water) or a continuous oil phase (e.g.,water-in-oil and oil-in-water-in-oil). The oil phase herein may comprisesilicone oils, non-silicone oils such as hydrocarbon oils, esters,ethers, and the like, and mixtures thereof.

The aqueous phase typically comprises water. However, in otherembodiments, the aqueous phase may comprise components other than water,including but not limited to water-soluble moisturizing agents,conditioning agents, anti-microbials, humectants and/or otherwater-soluble skin care actives. In one embodiment, the non-watercomponent of the composition comprises a humectant such as glycerinand/or other polyols. However, it should be recognized that thecomposition may be substantially (i.e., less than 1% water) or fullyanhydrous.

A suitable carrier is selected to yield a desired product form.Furthermore, the solubility or dispersibility of the components (e.g.,extracts, sunscreen active, additional components) may dictate the formand character of the carrier. In one embodiment, an oil-in-water orwater-in-oil emulsion is preferred.

Emulsions may further comprise an emulsifier. The composition maycomprise any suitable percentage of emulsifier to sufficiently emulsifythe carrier. Suitable weight ranges include from about 0.1% to about 10%or about 0.2% to about 5% of an emulsifier, based on the weight of thecomposition. Emulsifiers may be nonionic, anionic or cationic. Suitableemulsifiers are disclosed in, for example, U.S. Pat. Nos. 3,755,560,4,421,769, and McCutcheon's Detergents and Emulsifiers, North AmericanEdition, pages 317-324 (1986). Suitable emulsions may have a wide rangeof viscosities, depending on the desired product form.

The carrier may further comprise a thickening agent as are well known inthe art to provide compositions having a suitable viscosity andrheological character.

Optional Components

In some embodiments, the inventive composition herein may include one ormore optional components known for use in topical cosmetic compositions,provided the optional components do not unacceptably alter the desiredbenefits of the composition. The optional components, when present, maybe included at an amount of about 50%, 40%, 30%, 20%, 10%, 5%, or 3%, byweight of the composition, for example, at least about 0.001%, 0.01%,0.1%, 0.2%, 0.5%, or 1%, by weight of the composition. Suitable rangesinclude any combination of the lower and upper limits including suitableranges from about 0.1% to about 50%; from about 0.2% to about 20%; orfrom about 1% to about 10%, by weight of the composition.

The optional components, when incorporated into the composition, shouldbe suitable for use in contact with human skin tissue without unduetoxicity, incompatibility, instability, allergic response, and the like.Nonlimiting examples of optional components include additional skinanti-aging agents, skin tone agents, anti-inflammatory agents, sunscreenactives, anti-acne actives, desquamation actives, anti-cellulite agents,chelating agents, flavonoids, tanning active, non-vitamin antioxidantsand radical scavengers, hair growth regulators, anti-wrinkle actives,anti-atrophy actives, minerals, phytosterols and/or plant hormones,N-acyl amino acid compounds, antimicrobial or antifungal actives, andother useful skin care actives, which are described in further detail inU.S. Publication Nos. US2006/0275237A1 and US2004/0175347A1.

The Personal Care Product Council's International Cosmetic IngredientDictionary and Handbook, Thirteenth Edition, describes a wide variety ofnon-limiting cosmetic and pharmaceutical ingredients commonly used inthe skin care industry, which are suitable optional components for usein the compositions of the present invention. Examples of theseingredient classes include: abrasives, absorbents, aesthetic componentssuch as fragrances, pigments, colorings/colorants, essential oils,anti-caking agents, antifoaming agents, antimicrobials, binders,biological additives, buffering agents, bulking agents, chelatingagents, chemical additives, colorants, cosmetic astringents, cosmeticbiocides, denaturants, drug astringents, emollients, externalanalgesics, film formers or materials, opacifying agents, pH adjusters,preservatives, propellants, reducing agents, sequestrants, skin coolingagents, skin protectants, thickeners viscosity modifiers, vitamins, andcombinations thereof.

Suitable skin tone agents include, but are not limited to, sugar amines,arbutin, deoxyarbutin, 1,3-dihydroxy-4-alkylbenzene such ashexylresorcinol, sucrose dilaurante, bakuchoil (4-[(1E,3S)-3-ethenyl-3,7-dimethyl-1,6 octadienyl] phenol or monterpene phenol),pyrenoine (available from Biotech Marine, France), Panicum miliaceumseed extract, arlatone dioic acid, cinnamic acid, ferulic acid,achromaxyl, methyl nicotinamide, oil soluble licorice extract, folicacid, undecylenic acid (i.e., undecenoic acid), zinc undecylenate,thiamine (Vitamin B1) and its hydrochloride, L-tryptophan, Helianthusannuus (sunflower) and Vitis vinifera (grape) leaf extract, carnosine(i.e., dragosine), methyl gentisate, 1,2-hexandiol and 1,2-octandiol(i.e., combination sold as Symdiol 68 by Symrise AG, Germany), inositol,decylenoylphenylalanine (e.g., sold under the tradename Sepiwhite bySeppic, France), kojic acid, hexamidine compounds, salicylic acid, andretinoids including retinol and retinyl propionate.

One or more anti-inflammatory agents may be included in the presentcomposition for improving the appearance of hyperpigmentation resultingfrom skin inflammation. Transient inflammatory events triggeringhyperpigmentation and, more specifically, post-inflammatoryhyperpigmentation include, but are not limited to, acne lesions, ingrownhairs, scratches, insect bites, surfactant damage, allergens, andshort-term UV exposure. Inflammation induced hyperpigmentation includingpost-inflammatory hyperpigmentation may be managed by incorporating intothe compositions herein an anti-inflammatory agent. When present, thecompositions herein contain up to about 20%, 10%, 5%, 3%, or 1% byweight of the composition, of the anti-inflammatory agent. When present,the compositions herein contain at least about 0.001%, 0.01%, 0.1%,0.2%, 0.3%, 0.5%, or 1%, by weight of the composition, of theanti-inflammatory agent. Suitable ranges include any combination of thelower and upper limits. Suitable anti-inflammatory agents include, butare not limited to nonsteroidal anti-inflammatory agents (NSAIDSincluding but not limited to ibuprofen, naproxen, flufenamic acid,etofenamate, aspirin, mefenamic acid, meclofenamic acid, piroxicam andfelbinac), glycyrrhizic acid (also known as glycyrrhizin, glycyrrhixinicacid, and glycyrrhetinic acid glycoside) and salts such as dipotassiumglycyrrhizate, glycyrrhetenic acid, licorice extracts, bisabolol (e.g.,alpha bisabolol), manjistha (extracted from plants in the genus Rubia,particularly Rubia cordifolia), and guggal (extracted from plants in thegenus Commiphora, particularly Commiphora mukul), kola extract,chamomile, red clover extract, and sea whip extract (extracts from plantin the order Gorgonacea), derivatives of any of the foregoing, andmixtures thereof.

The compositions herein may include one or more sunscreen actives (orsunscreen agents) and/or ultraviolet light absorbers. Herein, “sunscreenactive” collectively includes sunscreen actives, sunscreen agents,and/or ultraviolet light absorbers. Sunscreen actives include bothsunscreen agents and physical sunblocks. Sunscreen actives may beorganic or inorganic. Examples of suitable sunscreen actives aredisclosed in Personal Care Product Council's International CosmeticIngredient Dictionary and Handbook, Thirteenth Edition, as “sunscreenagents.” Particularly suitable sunscreen actives are2-ethylhexyl-p-methoxycinnamate (commercially available as PARSOL™ MCX),4,4′-t-butyl methoxydibenzoyl-methane (commercially available as PARSOL™1789), 2-hydroxy-4-methoxybenzophenone, octyldimethyl-p-aminobenzoicacid, digalloyltrioleate, 2,2-dihydroxy-4-methoxybenzophenone,ethyl-4-(bis(hydroxypropyl))aminobenzoate,2-ethylhexyl-2-cyano-3,3-diphenylacrylate, 2-ethylhexyl-salicylate,glyceryl-p-aminobenzoate, 3,3,5-tri-methylcyclohexylsalicylate, menthylanthranilate, p-dimethyl-aminobenzoic acid or aminobenzoate,2-ethylhexyl-p-dimethyl-amino-benzoate, 2-phenylbenzimidazole-5-sulfonicacid, 2-(p-dimethylaminophenyl)-5-sulfonicbenzoxazoic acid, octocrylene,zinc oxide, benzylidene camphor and derivatives thereof, titaniumdioxide, and mixtures thereof.

In one embodiment, the composition may comprise from about 1% to about20%, and alternatively from about 2% to about 10% by weight of thecomposition, of the sunscreen active. Exact amounts will vary dependingupon the chosen sunscreen active and the desired Sun Protection Factor(SPF), which is within the knowledge of one of skilled in the art.

II. Methods of Use

Various methods of treatment, application, regulation, or improvementmay utilize the aforementioned compositions. Identification of a regionof aging skin may occur on any skin surface of the body. Skin surfacesof the most concern tend to be those not typically covered by clothingsuch as facial skin surfaces, hand and arm skin surfaces, foot and legskin surfaces, and neck and chest skin surfaces. In particular,identification of the region of aging skin may be on a facial skinsurface including the forehead, perioral, chin, periorbital, nose,and/or cheek skin surfaces. The target skin surface may include any signof skin aging known in the art (e.g., fine lines, deep lines, wrinkles,course texture, sagging, unfirm skin and lack of elasticity).

The method may include applying the composition to the previouslyidentified area of aging skin, or an area where one seeks to prevent theappearance of aging skin. Many regimens exist for the application of thecomposition. The composition may be applied at least once a day, twice aday, or on a more frequent daily basis, during a treatment period. Whenapplied twice daily, the first and second applications are separated byat least 1 to 12 hours. Typically, the composition may be applied in themorning and/or in the evening before bed.

The treatment period is ideally of sufficient time for the combinationof vitamin B₃ compound and artichoke leaf extract to provide animprovement in the appearance of aging skin. The treatment period may beat least 1 week, and in some embodiments the treatment period may lastabout 4 weeks, 8 weeks, or 12 weeks. In certain embodiments, thetreatment period will extend over multiple months (i.e., 3-12 months) ormultiple years. In one embodiment the composition is applied at leastonce a day during a treatment period of at least 4 weeks, 8 weeks, or 12weeks. In one embodiment the composition is applied twice a day during atreatment period of at least 4 weeks, 8 weeks, or 12 weeks.

The step of applying the composition may be accomplished by localizedapplication. In reference to application of the composition, the terms“localized”, “local”, or “locally” mean that the composition isdelivered to the targeted area (e.g., wrinkles around the eyes) whileminimizing delivery to skin surface not requiring treatment. Thecomposition may be applied and lightly massaged into area of aging skin.The form of the composition or the dermatologically acceptable carriershould be selected to facilitate localized application. While certainembodiments herein contemplate applying a composition locally to anarea, it will be appreciated that compositions herein can be appliedmore generally or broadly to one or more skin surfaces.

In some embodiments, the composition may be delivered by a variety ofapplicators appropriate for localized and general application. Suchapplicators can include droppers, applicator wands, cotton swabs, or anyother suitable device. Other suitable applicators include SH-0127 penapplicator available from Shya Hsin Plastic Works, Inc., Taiwan andeither the Xpress Tip or liquid filled swab available from SwabPlus,Inc., China. The applicator may be configured to easily apply thecomposition to signs of aging, such as fine lines and wrinkles, andallowing for a dosed amount of the composition of between about 1 toabout 50 uL/cm² or between about 1 to about 5 uL/cm². In anotherembodiment, the composition is applied to the one or more signs of agingand more generally to one or more facial skin surfaces contemporaneously(i.e., over a period of less than 30 minutes or, more typically, lessthan 5 minutes). It is to be appreciated that the compositions hereinmay also be applied directly by using one's finger or in otherconventional manners.

In one embodiment, the method comprises the steps of applying a firstcomposition comprising an effective amount of artichoke leaf extract andvitamin B₃ compound in combination to a skin surface and of applying asecond composition to the skin surface, before or after the firstcomposition. The first and second compositions may be any compositionsdescribed herein; however, the second composition may optionallycomprise an effective amount of the artichoke leaf extract and vitaminB₃ compound blend present in the first composition. The secondcomposition may comprise one or more anti-aging agents, tone agents,sunscreen actives, anti-inflammatory agents, or optional components. Thefirst composition may be generally or locally applied, while the secondcomposition may be generally or locally applied to the skin surfaceincluding the aging skin to which the first composition is applied. Incertain embodiments, the skin surface is facial skin surface whichinclude one or more of the forehead, perioral, chin, periorbital, nose,and cheek skin surfaces. In another embodiment, the first and secondcompositions are applied contemporaneously to at least the cheek,forehead, and chin/perioral skin surfaces. For general application to askin surface and, particularly a facial skin surface, the dosed amountof the first or second composition may be between about 1 to about 50uL/cm² per application (i.e., per single application to the skinsurfaces). In certain embodiments, the artichoke leaf extract andvitamin B₃ compound may be included in two separate compositions thatare used as part of a daily skin care regimen.

Suitable methods may comprise any one or more of the abovementionedsteps. All of the aforementioned steps are applicable to application,treatment, regulation, and/or improvement of aging skin appearance. Onesuitable method of improving the appearance of aging skin includes thestep of topically applying a composition comprising an effective amountof artichoke leaf extract and vitamin B₃ compound blend to the agingskin surface, wherein the composition is applied for a period of timesufficient to improve the appearance of the aging skin.

III. Mechanisms of Action

With aging, the protective function of the skin's epidermal barrier maybecome impaired. For example, the aging epidermal barrier may sufferincreased permeability to harmful stimuli (e.g., free radicals), areduction in the amount of lipid in the intercellular matrix, and/or adecreased capacity to diffuse toxins from deeper layers, which can leadto harmful stimuli penetrating the stratum corneum more easily. As aresult, the underlying dermal layers may suffer increased damage suchas, for example, degradation of collagen and elastin, and thinning ofthe stratum corneum. Thus, the recovery capacity of the epidermalbarrier is substantially reduced, and the effects of aging may becomevisibly evident by the appearance of, for example, fine lines, wrinkles,and/or other textural signs of skin aging.

Up-regulation of NF-κB is associated with inflammation, which leads toimpaired epidermal barrier function and the resulting appearance oftextural signs of skin aging. Conversely, inhibition of NF-κBcorresponds to an improved dermal matrix function, leading to improvedtextural appearance of the aging skin.

EXAMPLES Example 1—Exemplary Compositions

Table 1 sets forth non-limiting examples of compositions suitable foruse herein. The examples are given solely for the purpose ofillustration and are not to be construed as limitations herein, as manyvariations thereof are possible without departing from the spirit andscope of the invention, which would be recognized by one of ordinaryskill in the art. In the examples, all concentrations are listed asweight percent, unless otherwise specified and may exclude minormaterials such as diluents, filler, and so forth. The listedformulations, therefore, comprise the listed components and any minormaterials associated with such components. As is apparent to one ofordinary skill in the art, the selection of these minor materials willvary depending on the physical and chemical characteristics of theparticular ingredients selected to make the present invention asdescribed herein.

All examples may be used to treat or improve the appearance of one ormore signs of aging. The method herein may further relate to a regimeninvolving the localized treatment for one or more aging signs by a firstcomposition (e.g., Examples A or B) and a more broad or general facialskin treatment by a second composition (e.g., Examples C, D or E), whichcan be applied before or after the localized treatment to improve aparticular sign of aging (e.g., across the entire face).

TABLE 1 Exemplary Compositions Example Example Example Example ExampleComponent/% by wt. A B C D E Artichoke Leaf Extract (Bio-Benefity ™,available 1.00 3.50 3.00 3.5 3 from Ichimaru Pharcos Corp.) Niacinamide(CAS No. 98-92-0) 5.00 5.00 5.00 5.00 5.00 Olive Oil Extract (OLIVEM460, available from 0.00 0.00 0.03 0.1 0.25 B&T Company)N-Acetylglucosamine 0.00 0.00 2.00 0.00 0.00 Hexamidine Diisethionate0.00 0.00 0.09 0.09 0.00 Sepiwhite ™ (Undecylenoyl-phenylalanine, 0.000.00 0.50 0.50 0.00 neutralized) (available from SEPPIC) Sepigel 305 ™(Polyacrylamide + C13-14 isoparaffin + laureth-7) (available fromSEPPIC) 0.00 0.00 2.00 2.00 2.00 Dipotassium Glycyrrhizate 0.00 0.100.10 0.30 0.00 Homosalate 0.00 0.00 0.00 9.00 0.00 Avobenzone 0.00 0.000.00 3.00 0.00 Octocrylene 0.00 0.00 0.00 2.60 0.00 Oxybenzone 0.00 0.000.00 1.00 0.00 Octisalate 0.00 0.00 0.00 4.50 0.00 Butylene Glycol (CASNo. 107-88-0) 5.50 5.50 5.50 5.50 5.50 Glycerin (CAS No. 56-81-5) 2.502.50 7.50 7.50 10.00 DC 1503 Fluid ™ (available from DowCorning) 2.502.50 2.50 2.50 2.50 Lubrajel Oi1 ™ (available from Sederma) 1.44 1.441.44 1.44 1.44 Phenonip XB ™ (available from Clariant) 1.25 1.25 1.251.25 1.25 D-panthenol (CAS No. 81-13-0) 1.00 1.00 1.00 1.00 1.00Tospearl 2000 ™ (Polymethylsils esquioxane) (CAS No. 68554-70-1)(available from GE 1.00 1.00 1.00 1.00 1.00 Silicones/Momentive)DL-Alpha Tocopheryl Acetate (CAS No. 7695-91-2) 0.50 0.50 0.50 0.50 0.50Prodew 400 ™ (available from Ajinomoto) 0.50 0.50 0.50 0.50 0.50 PemulenTR-2 ™ (Acrylates/C10-30 Alkyl Acrylate 0.25 0.25 0.25 0.25 0.25Crosspolymer) (available from Noveon) Polysorbate 20 (CAS No. 9005-64-5)0.25 0.25 0.25 0.25 0.25 Sodium Metabisulfite (CAS No. 7681-57-4) 0.250.25 0.25 0.25 0.25 Allantoin (CAS No. 97-59-6) 0.20 0.20 0.20 0.20 0.20Sodium Hydroxide (CAS No. 1310-73-2) (50% 0.17 0.17 0.17 0.17 0.17solution by weight in water) Disodium EDTA (CAS No. 139-33-3) 0.10 0.100.10 0.10 0.10 Xanthan Gum (CAS No. 11138-66-2) 0.05 0.05 0.05 0.05 0.05Sodium Hyaluronate (CAS No. 9067-32-7) 0.01 0.01 0.01 0.01 0.01 Water(CAS No. 7732-18-5) QS QS QS QS QS TOTAL (% by weight of totalcomposition) 100.00 100.00 100.00 100.00 100.00

The compositions herein are generally prepared by conventional methodssuch as are known in the art of making topical compositions. Suchmethods typically involve mixing of the ingredients in one or more stepsto a relatively uniform state, with or without heating, cooling,application of vacuum, and the like. Typically, emulsions are preparedby first mixing the aqueous phase materials separately from the fattyphase materials and then combining the two phases as appropriate toyield the desired continuous phase. The compositions may be prepared tooptimize stability (physical stability, chemical stability,photostability) and/or delivery of the active materials. Thisoptimization may include appropriate pH (e.g., less than 7), exclusionof materials that can complex with the active agent and thus negativelyimpact stability or delivery (e.g., exclusion of contaminating iron),use of approaches to prevent complex formation (e.g., appropriatedispersing agents or dual compartment packaging), use of appropriatephotostability approaches (e.g., incorporation of sunscreen/sunblock,use of opaque packaging), etc.

Example 2—NF-κB Inhibition Analysis

In this Example, the effect of an artichoke-vitamin B₃ blend on NF-κBinhibition is evaluated. The vitamin B₃ compound used is niacinamide.

In Vitro Method.

CellSensor™ NF-κB-bla HEK 293T cells were pre-incubated for 1 hour withactives, stimulated with TNFα, and then incubated. After 5 hours plateswere analyzed with the ToxBLAzer Dual Screenkit from Invitrogen.

TABLE 2 Effect of Artichoke Leaf Extract and Vitamin B₃ Compound onNF-κB inhibition Artichoke Combination of Artichoke Expected AdditiveLeaf Niacinamide Leaf Extract 1.0% + Effect of Extract 1.0% 0.0005%Niacinamide0.0005% Combination [A] [B] [C] [Sum of A + B] % inhibition5% 47% 86%** 52% of NF- κB **Statistically significant p = 0.0237

As illustrated in Table 2, the combination of artichoke extract andvitamin B₃ compound synergistically increased the inhibition of NF-κB,which is associated with reduced inflammation, a healthy epidermalbarrier and healthy, younger looking skin.

Example 3—Method of Treatment

A test subject topically applies a composition comprising 3.5% artichokeleaf extract, 5.0% vitamin B₃ compound, and a dermatologicallyacceptable carrier to the entire face at least once per day for 12weeks. The subject's facial skin is evaluated at baseline, week 4, week8, and week 12 of treatment. With product use, the appearance of signsof facial skin aging such as fine lines and wrinkles are reduced, asassessed by digital imaging, expert grading and/or self assessment.

The dimensions and values disclosed herein are not to be understood asbeing strictly limited to the exact numerical values recited. Instead,unless otherwise specified, each such dimension is intended to mean boththe recited value and a functionally equivalent range surrounding thatvalue. For example, a dimension disclosed as “40 mm” is intended to mean“about 40 mm.”

Every document cited herein, including any cross referenced or relatedpatent or application, is hereby incorporated herein by reference in itsentirety unless expressly excluded or otherwise limited. The citation ofany document is not an admission that it is prior art with respect toany invention disclosed or claimed herein or that it alone, or in anycombination with any other reference or references, teaches, suggests ordiscloses any such invention. Further, to the extent that any meaning ordefinition of a term in this document conflicts with any meaning ordefinition of the same term in a document incorporated by reference, themeaning or definition assigned to that term in this document shallgovern.

While particular embodiments herein have been illustrated and described,it would be obvious to those skilled in the art that various otherchanges and modifications can be made without departing from the spiritand scope of the invention. It is therefore intended to cover in theappended claims all such changes and modifications that are within thescope of this invention.

What is claimed is:
 1. A method of improving the appearance of agingskin comprising: a. identifying a target portion of skin that exhibits asign of aging skin; and b. applying a composition comprising 0.05% to5%, by weight, of an artichoke leaf extract and 0.0001% to 15%, byweight, of a vitamin B₃ compound in combination to the target portion ofskin for a period of time sufficient for the combination of artichokeleaf extract and vitamin B₃ compound to synergistically increase theinhibition of NF-kB.
 2. The method of claim 1, wherein the portion ofskin surface is facial skin.
 3. The method of claim 2, wherein thefacial skin is selected from the group consisting of forehead, perioral,chin, periorbital, nose, and cheek skin surfaces.
 4. The method of claim1, wherein the composition is applied at least once a day for at leastfour weeks.
 5. The method of claim 1, wherein the vitamin B₃ compound isniacinamide.
 6. The method of claim 1, wherein the composition furthercomprises at least one additional skin active selected from the groupconsisting of sunscreen actives, anti-inflammatory agents and skin toneactives.
 7. The method of claim 1, wherein the improvement to theappearance of aged skin is selected from the group consisting ofimproving the appearance of wrinkles and coarse deep wrinkles, finelines, skin lines, crevices, bumps, unevenness, roughness, loss of skinelasticity, sagging, unfirm skin, keratoses; abnormal differentiation,hyperkeratinization; elastosis, and collagen breakdown.
 8. The method ofclaim 1, wherein the composition has a pH of less than 7 and excludesmaterials that can complex with the vitamin B3 compound and theartichoke leaf extract.